Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis

Mader, Marius Marc-Daniel; Czorlich, Patrick; König, Christina; Fuhrmann, Valentin; Kluge, Stefan; Westphal, Manfred; Grensemann, Jörn

doi:10.1007/s00701-018-3680-z

Cited by 19 publications

(27 citation statements)

References 29 publications

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“…Antibiotic concentrations are usually measured in serum and do not reflect the concentrations at the infectious focus that should be above the MIC to allow for a continuous bactericidal effect. Meropenem's penetration for peritoneal fluid is of approximately 70% [31], but only 25% for lung epithelial lining fluid and lung tissue [45,46] and 20% for cerebrospinal fluid [47]. In cases of low penetration, it has been doubted that sufficient concentrations are attained for a sustained bactericidal effect [45].…”

Section: Discussionmentioning

confidence: 99%

Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

Grensemann

Busse

König

et al. 2020

Ann. Intensive Care

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Background: Infection and sepsis are a main cause of acute-on-chronic liver failure (ACLF). Adequate dosing of antimicrobial therapy is of central importance to improve outcome. Liver failure may alter antibiotic drug concentrations via changes of drug distribution and elimination. We studied the pharmacokinetics of meropenem in critically ill patients with ACLF during continuous veno-venous hemodialysis (CVVHD) and compared it to critically ill patients without concomitant liver failure (NLF). Methods: In this prospective cohort study, patients received meropenem 1 g tid short-term infusion (SI). Meropenem serum samples were analyzed by high-performance liquid chromatography. A population pharmacokinetic analysis was performed followed by Monte Carlo simulations of (A) meropenem 1 g tid SI, (B) 2 g loading plus 1 g prolonged infusion tid (C) 2 g tid SI, and (D) 2 g loading and continuous infusion of 3 g/day on days 1 and 7. Probability of target attainment (PTA) was assessed for 4× the epidemiological cutoff values for Enterobacterales (4 × 0.25 mg/L) and Pseudomonas spp. (4 × 2 mg/L). Results: Nineteen patients were included in this study. Of these, 8 patients suffered from ACLF. A two-compartment model with linear clearance from the central compartment described meropenem pharmacokinetics. The peripheral volume of distribution (V 2) was significantly higher in ACLF compared to NLF (38.6L versus 19.7L, p = .05). PTA for Enterobacterales was achieved in 100% for all dosing regimens. PTA for Pseudomonas spp.

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Section: Discussionmentioning

confidence: 99%

Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

Grensemann

Busse

König

et al. 2020

Ann. Intensive Care

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“…El rango lineal es menor que el establecido por el fabricante para la determinación de VAN en suero/plasma (4,0 -80,0 µg/mL); sin embargo, el LOQ obtenido en nuestro trabajo es menor. Debido a la gran variabilidad interindividual reportada para la penetración de VAN al SNC, sumada a la dependencia existente de acuerdo con la patología subyacente y a los distintos esquemas de administración de VAN (17)(18) , no se ha podido establecer un valor de referencia para la concentración terapéutica de VAN en LCR, aunque, ciertos autores, sugieren una concentración deseada entre 5-20 µg/mL (19) . La gran variabilidad de la concentración de VAN en LCR dada por factores como la terapia esteroidea concomitante (20) , pacientes sin inflamación meníngea, o pacientes en estado crítico de salud; es reflejada por la relación LCR/plasma que va de 0,00 a 0,81 (21) .…”

Section: Discussionunclassified

Validación de un método inmunológico para la determinación de vancomicina en líquido cefalorraquídeo.

Marks

Duchein²,

Gonzalez

et al. 2019

Rev Fac Cien Med Univ Nac Cordoba

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<p>Introducción: La vancomicina (VAN) es un antibiótico utilizado para el tratamiento de infecciones graves. Su uso está relacionado con efectos adversos como hiperemia facial aguda, nefrotoxicidad y ototoxicidad. Al tener un rango terapéutico muy estrecho, el monitoreo terapéutico resulta necesario para maximizar la eficiencia y minimizar los efectos tóxicos. Se estima que su concentración en LCR es, aproximadamente, un 10% de la plasmática en pacientes que reciben tratamiento endovenoso del mismo y que presentan inflamación de las meninges. Las concentraciones plasmáticas de VAN no son un indicador confiable de las presentes en LCR. El objetivo de este trabajo fue validar un método inmunológico basado en la interacción cinética de micropartículas en solución (KIMS) para la determinación de VAN en LCR. Materiales y Métodos: Se validó el método KIMS para la valoración de VAN en LCR. Para ello, se determinaron los parámetros de linealidad, precisión, exactitud, límite de detección, límite de cuantificación, interferencia, selectividad y especificidad. Resultados: el método fue lineal en un intervalo entre 0 y 15 µg/mL, los CV% obtenidos oscilaron entre 0,7 y 2,5% en el rango lineal. Los LOD y LOQ fueron 0,4 µg/mL y 1,4 µg/mL respectivamente. La ecuación de la recta obtenida en base a la correlación de métodos entre KIMS y HPLC-UV fue y= 0,9151x + 1,1695, R²=0,9453. Conclusión: El método KIMS demostró tener una sensibilidad y especificidad apropiadas para la determinación de VAN en LCR y, ser una herramienta útil para el monitoreo de pacientes que presenten infecciones complicadas a nivel del SNC.</p>

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“…5,17,30,34,36 In the analysis of dosing regimens for the intravenous administration of meropenem, the posologic regimen reported in studies mentioned infusions that ranged from 1 to 2 g every 6, 8 or 12 h, totalling 3 to 6 g/day. 22,33,35,[39][40][41] Doses were often higher if the patient had a severe infection or a bacterium with high MIC. 16 The meropenem infusion can be continuous (for 24 h) or prolonged.…”

Section: Re Sultsmentioning

confidence: 99%

“…16,27,30,38,48 The samples preparation consisted of precipitation of plasma proteins with acetonitrile or metanol. 21,33,40 Recent studies applied ultrafiltration to analyse only the unbound fraction. 35,49 There are no available commercial kits for meropenem TDM or any other beta-lactam such as those required for immunological assaying TA B L E 1 Summary characteristics from studies included in this review in closed systems and automated chains as for other drugs (e.g.…”

Section: Re Sultsmentioning

confidence: 99%

Meropenem use and therapeutic drug monitoring in clinical practice: a literature review

et al. 2021

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What is known and objective: Meropenem, a carbapenem antibiotic, is widely prescribed for the treatment of life-threatening infections. The main parameter associated with its therapeutic success is the percentage of time that the levels remain above the minimum inhibitory concentration. Inadequate levels of meropenem can lead to therapeutic failure and increase the possibility of microbial resistance. The employment of strategies involving dose regimens and drug pharmacodynamics has become increasingly important to optimize therapies. In the present study, we conducted a review with the purpose of assembling information about the clinical use of meropenem and therapeutic drug monitoring. Methods:A literature review emphasizing the application of therapeutic drug monitoring (TDM) of meropenem in clinical practice has been done. To identify articles related to the topic, we performed a standardized search from January 21, 2020 to December 21, 2020, using specific descriptors in PubMed, Lilacs and Embase.Results and discussion: In total, 35 studies were included in the review. The daily dose of meropenem commonly ranged from 3 to 6 g/day. Critically ill patients and those with impaired renal function appear to be the most suitable patients for the application of meropenem TDM, in order to guide therapy. We observed that most of the studies recommend TDM and that, in nine locations, the TDM of meropenem and of other beta-lactams is a routine practice. TDM data can help to maximize the clinical outcomes of the treatment with meropenem. It can also improve the patient care by providing suitable levels of meropenem, guiding the most appropriate dose regimens, which is the main parameter associated with therapeutic success. What is new and conclusion:The findings from this review suggest that the therapeutic monitoring of meropenem can be beneficial, since it adjusts the treatment and aids clinical outcomes. It does so by indicating the appropriate dosage and preventing failure, toxicity and possible antimicrobial resistance. The multidisciplinary effort, basic knowledge and communication among the medical team are also essential.

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Intrathecal penetration of meropenem and vancomycin administered by continuous infusion in patients suffering from ventriculitis—a retrospective analysis

Cited by 19 publications

References 29 publications

Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

Acute-on-chronic liver failure alters meropenem pharmacokinetics in critically ill patients with continuous hemodialysis: an observational study

Validación de un método inmunológico para la determinación de vancomicina en líquido cefalorraquídeo.

Meropenem use and therapeutic drug monitoring in clinical practice: a literature review

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